A5100678848- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- melanin and skin pigmentation
- Epigenetics and DNA Methylation
- Hippo pathway signaling and YAP/TAZ
- Genetic and Kidney Cyst Diseases
- RNA Research and Splicing
- RNA modifications and cancer
- Cell death mechanisms and regulation
- Pharmacological Effects of Natural Compounds
- Glycosylation and Glycoproteins Research
- Heat shock proteins research
- Alzheimer's disease research and treatments
- Calcium signaling and nucleotide metabolism
- Immune cells in cancer
- Peroxisome Proliferator-Activated Receptors
- Hedgehog Signaling Pathway Studies
- Sirtuins and Resveratrol in Medicine
- Advanced Polymer Synthesis and Characterization
- Microtubule and mitosis dynamics
- Phagocytosis and Immune Regulation
- Sphingolipid Metabolism and Signaling
- Plant responses to water stress
- interferon and immune responses
University of Cambridge
2018-2024
Andong National University
2022-2023
Wellcome Trust
2018-2022
UK Dementia Research Institute
2021-2022
Tokyo Institute of Technology
2020
Daejeon University
2019-2020
Seoul National University
2016-2020
RIKEN
2020
Lotte Fine Chemical (South Korea)
2020
RIKEN Advanced Science Institute
2020
Abstract Contact inhibition enables noncancerous cells to cease proliferation and growth when they contact each other. This characteristic is lost undergo malignant transformation, leading uncontrolled solid tumor formation. Here we report that autophagy compromised in contact-inhibited 2D or 3D-soft extracellular matrix cultures. In such cells, YAP/TAZ fail co-transcriptionally regulate the expression of myosin-II genes, resulting loss F-actin stress fibers, which impairs autophagosome The...
Excessive mitochondrial fission is a prominent early event and contributes to dysfunction, synaptic failure, neuronal cell death in the progression of Alzheimer's disease (AD). However, it remains be determined whether inhibition excessive beneficial mammal models AD. To determine dynamin-related protein 1 (Drp1), key regulator fragmentation, can disease-modifying therapeutic target for AD, we examined effects Drp1 inhibitor on dysfunctions induced by oligomeric amyloid-β (Aβ) neurons...
Highlights•Leucine metabolizing enzymes impact mTORC1 activity•AcCoA, the final leucine metabolite, regulates activity by Raptor acetylation•AcCoA in a cell-type-specific manner•Fasted tissues mice have decreased AcCoA, acetylated Raptor, and activitySummaryThe mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is master regulator cell growth metabolism. Leucine (Leu) activates many tried to identify mechanisms whereby cells sense Leu this context. Here we describe that metabolite...
Abstract The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator cell growth, metabolism and autophagy. Multiple pathways modulate mTORC1 in response to nutrients. Here we describe that nucleus–cytoplasmic shuttling p300/EP300 regulates activity amino acid or glucose levels. Depletion these nutrients causes cytoplasm-to-nucleus relocalization p300 decreases acetylation the component raptor, thereby reducing activating This mediated by AMP-activated protein...
Background Autophagy has paradoxical and complex functions in cancer development, autophagy-related genes (ATG) are key regulators autophagy. Until now, more than 30 different ATG proteins have been identified yeast, their mammalian counterparts also reported. Although the roles of a few characterized, role ATG10 is almost completely unknown. Methodology/Principal Findings To investigate clinicopathological colorectal cancer, we analyzed expression tissues cell lines. Protein analysis showed...
Abstract Mitochondria play a pivotal role in cancer bioenergetics and are considered potential target for anticancer therapy. Considering the limited efficacy toxicity of currently available mitochondria-targeting agents, it is necessary to develop effective drugs. By screening large chemical library consisting natural products with diverse entities, we identified gracillin, steroidal saponin, as antitumor drug. Gracillin displayed broad-spectrum inhibitory effects on viability panel human...
Mitochondrial dynamics and mitophagy are thought to be important events for the quality control of mitochondria mitochondria‐associated diseases. To identify novel modulators, we developed a cell‐based screening system selected 1,10‐phenanthroline (Phen) as target molecule. Phen treatment highly induced mitochondrial fragmentation dysfunctions in Drp1 dependent manner. also increased autophagy. Moreover, prolonged exposure clearance through mitophagy. Phen‐mediated loss mass was more reduced...
Summary Mitochondrial dynamics control mitochondrial functions as well their morphology. However, the role of in melanogenesis is largely unknown. Here, we show that regulate by modulating ROS ‐ ERK signaling pathway. Genetic and chemical inhibition D rp1, a fission protein, increased melanin production elongation melanocytes melanoma cells. In contrast, down‐regulation OPA1, mitochondria fusion regulator, suppressed melanogensis but induced massive fragmentation hyperpigmented Consistently,...
Quality control of peroxisomes is essential for cellular homeostasis. However, the mechanism underlying pexophagy largely unknown. In this study, we identified HSPA9 as a novel regulator. Downregulation increased macroautophagy/autophagy but decreased number in vitro and vivo. The loss by depletion was attenuated SQSTM1-deficient cells. HSPA9-deficient cells, level peroxisomal reactive oxygen species (ROS) increased, while inhibition ROS blocked HeLa SH-SY5Y Importantly, reconstitution...
Excessive mitochondrial fission is associated with the pathogenesis of neurodegenerative diseases. Dynamin-related protein 1 (Drp1) possesses specific activity in mitochondria and peroxisomes. Various post-translational modifications Drp1 are known to modulate complex dynamics. However, post-transcriptional regulation remains poorly understood. Here, we show that heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) regulates expression at level. hnRNP directly interacts mRNA its 3'UTR...
Abstract As a dynamic organelle, mitochondria continuously fuse and divide with adjacent mitochondria. Imbalance in dynamics leads to their dysfunction, which implicated neurodegenerative diseases. However, how alteration glucose defect contribute pathogenesis of Alzheimer’s disease (AD) is still largely unknown. Dynamin‐related protein 1 (Drp1) an essential regulator for fission. Among various posttranslational modifications, O -GlcNAcylation plays role as sensor nutrient oxidative stress....
Autophagy is a cooperative process between autophagosomes and lysosomes that degrades cellular organelles. Although autophagy regulates the turnover of components, its role in melanogenesis not clearly established. Previously, we reported ARP101 induces various cancer cells. Here, show inhibits by regulation autophagy. inhibited α‐MSH‐stimulated melanin synthesis suppressed expression tyrosinase TRP1 immortalized mouse melanocytes. also induced Knockdown ATG5 reduced both anti‐melanogenic...
// Yoon Kyung Jo 1 , Na Yeon Park So Jung Byung-Gyu Kim 2 Ji Hyun Shin Doo Sin Dong-Jun Bae 3 Young-Ah Suh Jeong Ho Chang 4 Eun Lee 5 Sang-Yeob Jin Cheon 3, 6 Dong-Hyung Cho Department of Gerontology, Graduate School East-West Medical Science, Hee University, Yongin, South Korea Leading-edge Research Center for Drug Discovery and Development Diabetes Metabolic Disease, Medicine, Kyungpook National University Hospital, Daegu, Asan Institute Life Sciences, Center, Seoul, Biology Education,...
Several studies have shown that dysfunction of macroautophagy/autophagy is associated with many human diseases, including neurodegenerative disease and cancer. To explore the molecular mechanisms autophagy, we performed a cell-based functional screening SH-SY5Y cells stably expressing GFP-LC3, using an siRNA library identified TMED10 (transmembrane p24 trafficking protein 10), previously known as γ-secretase-modulating protein, novel regulator autophagy. Further investigations revealed...
Abstract The factors regulating cellular identity are critical for understanding the transition from health to disease and responses therapies. Recent literature suggests that autophagy compromise may cause opposite effects in different contexts by either activating or inhibiting YAP/TAZ co-transcriptional regulators of Hippo pathway via unrelated mechanisms. Here, we confirm perturbation cell types can growth-promoting oncogenic transcriptional signalling. These apparently contradictory be...
Autophagy is associated with cell survival and death. implicated in the pathophysiology of various human diseases. In order to identify autophagy regulatory molecules, we screened a chemical drug library SH-SY5Y cells selected Sertindole as potent inducer. was developed an antipsychotic for Schizophrenia. treatment highly induced formation autophagosomes well LC3 conversion. Subsequently, Sertindole-induced efficiently suppressed by down regulation ATG5. also increased reactive oxygen...
Purpose KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous inhibitors that failed to show clinical benefit during treatment breast cancer, can potentially overcome the therapeutic limitations current through inhibition both The present study further evaluates activity mechanism in vitro vivo. Materials Methods antitumor effect triple negative cancer (TNBC) cell lines was determined by MTT assay. Wound healing immunofluorescence assays were performed evaluate action...